DC-SIGN, a Dendritic Cell–Specific HIV-1-Binding Protein that Enhances trans-Infection of T Cells

Geijtenbeek, Teunis B. H.; Kwon, Douglas S.; Torensma, Ruurd; Vliet, Sandra J. van; Duijnhoven, G.C.F. van; Middel, Jeena; Cornelissen, I.L.M.H.A.; Nottet, Hans S.L.M.; KewalRamani, Vineet N.; Littman, Dan R.; Figdor, Carl G.; Kooyk, Yvette van

doi:10.1016/s0092-8674(00)80694-7

Cited by 2,177 publications

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“…These data imply that immature DC and LC in contrast to their mature forms are more important in HIV-1 transmission. Viral endocytosis leads to partial acid-proteolytic degradation in the late endosome, although some virus may be retained in its infectious state for longer periods [27,28] [26]. However, HIV entry via fusion leads to de novo productive infection first detectable at 24 h and with a plateau in vitro at 72 h. Recent studies suggest this de novo produced virus can re-enter the same or adjacent DC by endocytosis and the latter can also be infected de novo, thus mixing up the initial two distinct phases of viral endocytic degradation and de novo infection.…”

Section: Subsets In Hiv-1 Transmissionmentioning

confidence: 99%

“…Although similar mechanisms were assumed to be involved in LC transmission of HIV-1, it is becoming evident that LC might have a more complicated role in transmission [25]. Monocyte-derived DC capture HIV through the CLR DC-SIGN [26] and, to lesser degrees, mannose receptor and heparin sulphate proteoglycan syndecan-3 [27]. HIV-1 is either endocytosed or transferred directly to CD4 and CCR5 resulting in viral-cell membrane fusion and infection.…”

Section: Subsets In Hiv-1 Transmissionmentioning

confidence: 99%

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Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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Section: Subsets In Hiv-1 Transmissionmentioning

confidence: 99%

Section: Subsets In Hiv-1 Transmissionmentioning

confidence: 99%

Langerhans cells and viral immunity

2008

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“…DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].…”

Section: Introductionmentioning

confidence: 99%

“…Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21].…”

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confidence: 99%

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

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Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/ chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-a, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP. IntroductionThe C-type lectin dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) is a pathogen recognition receptor that interacts with mannose residues of glycoproteins in a calciumdependent manner via its C-terminal carbohydrate recognition domain [1,2]. DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles. The routes of HPV-16 L1-VLP entry in DC and the nature of cellular receptors involved in capture have been studied but remain to be fully characterized. HPV VLP Here, we report that HPV-16 L1-VLP particles bind to DC-SIGN in transfected cell lines, and to a lesser extent in DC, and that this interaction participates in L1-VLPinduced activation of DC. Thus, DC-SIGN is likely involved in DC activation by HPV VLP. Results and discussion HPV L1-VLP bind to DC-SIGN in DC-SIGN-transfected cell linesTo study interactions between L1-VLP and DC-SIGN, we...

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“…It is noted that certain effector functions are also subjected to regulation by miRNAs. C-type lectin DC-SIGN can mediate binding of certain viral and fungal pathogens (Geijtenbeek et al, 2000;Lanoue et al, 2004). During LPS-mediated moDC maturation, miR-155 is up-regulated.…”

Section: Mirnas Regulate Effector Function By Modcsmentioning

confidence: 99%